{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:16:39Z","timestamp":1788542199258,"version":"build-2803163510"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Union Commission\u2019s Seventh Framework","award":["305507"],"award-info":[{"award-number":["305507"]}]},{"name":"IMI2-CARDIATEAM","award":["821508"],"award-info":[{"award-number":["821508"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>The dilated cardiomyopathy (DCM) phenotype is the result of combined genetic and acquired triggers. Until now, clinical decision-making in DCM has mainly been based on ejection fraction (EF) and NYHA classification, not considering the DCM heterogenicity. The present study aimed to identify patient subgroups by phenotypic clustering integrating aetiologies, comorbidities, and cardiac function along cardiac transcript levels, to unveil pathophysiological differences between DCM subgroups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We included 795 consecutive DCM patients from the Maastricht Cardiomyopathy Registry who underwent in-depth phenotyping, comprising extensive clinical data on aetiology and comorbodities, imaging and endomyocardial biopsies. Four mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: [PG1] mild systolic dysfunction, [PG2] auto-immune, [PG3] genetic and arrhythmias, and [PG4] severe systolic dysfunction. RNA-sequencing of cardiac samples (n\u2009=\u200991) revealed a distinct underlying molecular profile per PG: pro-inflammatory (PG2, auto-immune), pro-fibrotic (PG3; arrhythmia), and metabolic (PG4, low EF) gene expression. Furthermore, event-free survival differed among the four phenogroups, also when corrected for well-known clinical predictors. Decision tree modelling identified four clinical parameters (auto-immune disease, EF, atrial fibrillation, and kidney function) by which every DCM patient from two independent DCM cohorts could be placed in one of the four phenogroups with corresponding outcome (n\u2009=\u2009789; Spain, n\u2009=\u2009352 and Italy, n\u2009=\u2009437), showing a feasible applicability of the phenogrouping.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The present study identified four different DCM phenogroups associated with significant differences in clinical presentation, underlying molecular profiles and outcome, paving the way for a more personalized treatment approach.<\/jats:p>\n                  <jats:p\/>\n               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Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8408-363X","authenticated-orcid":false,"given":"Fernando","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Puerta de Hierro , Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades in Cardiovascular Diseases (CIBERCV) , Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Center, Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel T H M","family":"Henkens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute (CARIM), Maastricht University Medical Center , PO Box 5800, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel E","family":"Adriaens","sequence":"additional","affiliation":[{"name":"Maastricht Centre for Systems Biology, Maastricht University , Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-7178","authenticated-orcid":false,"given":"Mark R","family":"Hazebroek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute (CARIM), Maastricht University Medical Center , PO Box 5800, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0457-9489","authenticated-orcid":false,"given":"Marco","family":"Mas\u00e8","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of 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J","family":"Derks","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Center, Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"van den Wijngaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Center, Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid P C","family":"Krapels","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Center, Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han G","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Center, Maastricht , The Netherlands"},{"name":"Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center , Nijmegen"},{"name":"GROW Institute for Developmental Biology and Cancer, Maastricht University Medical Centre , Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Sinagra","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-2257","authenticated-orcid":false,"given":"Pablo","family":"Garcia-Pavia","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Puerta de Hierro , Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades in Cardiovascular Diseases (CIBERCV) , Madrid, Spain"},{"name":"Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcon , 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